S100A4 blockage alleviates agonistic anti-CD137 antibody-induced liver pathology without disruption of antitumor immunity.

ABSTRACT: Liver-related autoimmune toxicities triggered by agonistic anti-CD137 antibodies have greatly limited their use in clinical applications. Here, we found that anti-CD137 monoclonal antibody (mAb) treatment in mice induced the infiltration of a large number of S100A4⁺ macrophages into the liver. Depletion of these cells or deficiency of S100A4 decreased inflammatory cytokine profiles and drastically reduced the number of liver pathogenic CD8⁺ T cells. Mechanistically, soluble S100A4 directly activated the Akt pathway and specifically prolonged CD8⁺ T cell survival. Interestingly, one S100A4 neutralizing mAb selectively alleviated liver abnormalities but did not affect the antitumor immunity induced by anti-CD137 mAb therapy. Thus, our study presents a novel m

SUBMITTER: Zhang J 

PROVIDER: S-EPMC5889198 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature